Effects of selective and non-selective ℵ-opioid receptor agonists on cutaneous C-fibre-evoked responses of rat dorsal horn neurones

Abstract

We have studied the effects of 3 putative ℵ-opioid receptor agonists, U50488H, ethylketocyclazocine (EKC) and dynorphin A 1–13 (DYN) on the processing of nociceptive information in the dorsal horn of the rat under halothane anaesthesia. Extracellular single unit recordings were made from convergent or multireceptive lumbar dorsal horn neurones, which could be excited by impulses in Aβ and C fibre afferents following transcutaneous electrical stimulation of their ipsilateral hind paw receptive fields and also by noxious and innocuous natural stimuli. Agonists were applied directly onto the surface of the spinal cord. DYN and U50488H consistently produced both a facilitation and inhibition of the C-fibre evoked nociceptive responses of individual cells, these dual effects being relatively insensitive to naloxone antagonism and cancelled each other for the whole population of cells. Aβ fibre-evoked responses were little altered. In contrast, EKC consistently depressed C-fibre transmission in a dose-dependent, naloxone reversible manner, analagous to, but considerably less potent than intrathecal morphine under identical experimental conditions. Agonist-induced effects on neuronal responses to natural stimulation (noxious pinch and innocuous prod) were consistent with the changes observed with the electrically evoked responses. The present results therefore indicate that EKC probably exerts its spinal antinociceptive activity in the rat spinal cord in a manner akin to μ-receptor activation. Results with U50488H and DYN indicate that χ-opioids can excite and inhibit individual neurones but produce no overall change on the whole population, so differing from effects mediated by the other opiate receptors.